Biomedical subjects

S E Middleton

Publications and source records attributed to S E Middleton.

7 recordsLinked to original sources

PubMed2005

Radiosurgery planning supported by the GEMSS grid.

GEMSS (Grid Enabled Medical Simulation Services IST-2001-37153) is an EU project funded to provide a test bed for Grid-enabled health applications. Its purpose is evaluation of Grid computing in the health sector. The health context imposes particular constraints on Grid infrastructure design, and it is this that has driven the feature set of the middleware. In addition to security, the time critical nature of health applications is accommodated by a Quality of Service component, and support for a well defined business model is also included. This paper documents experience of a GEMSS compliant radiosurgery application running within the Medical Physics department at the Royal Hallamshire Hospital in the UK. An outline of the Grid-enabled RAPT radiosurgery application is presented and preliminary experience of its use in the hospital environment is reported. The performance of the software is compared against GammaPlan (an industry standard) and advantages/disadvantages are highlighted. The RAPT software relies on features of the GEMSS middleware that are integral to the success of this application, and together they provide a glimpse of an enabling technology that can impact upon patient management in the 21st century.

Decision Support Systems, Clinical↗

PubMed2005

GEMSS: grid-infrastructure for medical service provision.

OBJECTIVES: The European GEMSS Project is concerned with the creation of medical Grid service prototypes and their evaluation in a secure service-oriented infrastructure for distributed on demand/supercomputing. Key aspects of the GEMSS Grid middleware include negotiable QoS support for time-critical service provision, flexible support for business models, and security at all levels in order to ensure privacy of patient data as well as compliance to EU law. METHODS: The GEMSS Grid infrastructure is based on a service-oriented architecture and is being built on top of existing standard Grid and Web technologies. The GEMSS infrastructure offers a generic Grid service provision framework that hides the complexity of transforming existing applications into Grid services. For the development of client-side applications or portals, a pluggable component framework has been developed, providing developers with full control over business processes, service discovery, QoS negotiation, and workflow, while keeping their underlying implementation hidden from view. RESULTS: A first version of the GEMSS Grid infrastructure is operational and has been used for the set-up of a Grid test-bed deploying six medical Grid service prototypes including maxillo-facial surgery simulation, neuro-surgery support, radio-surgery planning, inhaled drug-delivery simulation, cardiovascular simulation and advanced image reconstruction. CONCLUSIONS: The GEMSS Grid infrastructure is based on standard Web Services technology with an anticipated future transition path towards the OGSA standard proposed by the Global Grid Forum. GEMSS demonstrates that the Grid can be used to provide medical practitioners and researchers with access to advanced simulation and image processing services for improved preoperative planning and near real-time surgical support.

Access to Information↗

PubMed2005

GEMSS: privacy and security for a medical Grid.

OBJECTIVES: The GEMSS project is developing a secure Grid infrastructure through which six medical simulations services can be invoked. We examine the legal and security framework within which GEMSS operates. METHODS: We provide a legal qualification to the operations performed upon patient data, in view of EU directive 95/46, when using medical applications on the GEMSS Grid. We identify appropriate measures to ensure security and describe the legal rationale behind our choice of security technology. RESULTS: Our legal analysis demonstrates there must be an identified controller (typically a hospital) of patient data. The controller must then choose a processor (in this context a Grid service provider) that provides sufficient guarantees with respect to the security of their technical and organizational data processing procedures. These guarantees must ensure a level of security appropriate to the risks, with due regard to the state of the art and the cost of their implementation. Our security solutions are based on a public key infrastructure (PKI), transport level security and end-to-end security mechanisms in line with the web service (WS Security, WS Trust and SecureConversation) security specifications. CONCLUSION: The GEMSS infrastructure ensures a degree of protection of patient data that is appropriate for the health care sector, and is in line with the European directives. We hope that GEMSS will become synonymous with high security data processing, providing a framework by which GEMSS service providers can provide the security guarantees required by hospitals with regard to the processing of patient data.

Access to Information↗

PubMed2001

AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.

A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homology to the rat orphan receptor GPR54, was cloned from a human brain cDNA library. Heterologous expression of AXOR12 in mammalian cells permitted the identification of three surrogate agonist peptides, all with a common C-terminal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of which prevents metastasis in melanoma cells. Quantitative reverse transcriptase-polymerase chain reaction was used to study the expression of AXOR12 and KiSS-1 in a variety of tissues. The highest levels of expression of AXOR12 mRNA were observed in brain, pituitary gland, and placenta. The highest levels of KiSS-1 gene expression were observed in placenta and brain. A polyclonal antibody raised to the C terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression patterns and the nature of the putative cognate ligand for AXOR12 are discussed.

Amino Acid Sequence↗

PubMed1998

Thymus-dependent, anti-CD4-induced tolerance to rat cardiac allografts.

BACKGROUND: Treatment with anti-CD4 monoclonal antibodies (mAbs) leads to induction of transplant tolerance in rodent models, but the cellular mechanisms responsible are poorly defined. In this study, we used a rat model of cardiac transplantation to examine the contribution of the thymus gland to anti-CD4 mAb-induced tolerance. METHODS: Pretransplant administration of OX38 mAb partially depletes peripheral CD4 T cells and induces tolerance to fully allogeneic Lewis (RT1l) heterotopic cardiac allografts in DA (RT1a) recipients. Using this experimental model, the contribution of the adult thymus gland and of recent thymic emigrants to tolerance induction was assessed, and the cellular and humoral alloimmune responses accompanying tolerance defined. RESULTS: OX38 mAb selectively depleted mature CD4 T cells but spared CD4 T cells that had recently emerged from the thymus. Pretransplant thymectomy abrogated tolerance induction, but the data suggested a role for recent thymic emigrants rather than for the thymus gland per se. Both nonrejecting cardiac allografts in OX38-treated recipients and rejecting grafts in control animals were infiltrated to a similar extent by mononuclear cells, including activated T cells. Intragraft mRNA transcripts for interleukin (IL)-2, interferon-gamma, IL-4, IL-10, and IL-13 were similar in non-rejecting and rejecting allografts although, with the exception of IL-2, there was a trend towards reduced cytokine transcripts in tolerant grafts. CD4 T cells from long-term tolerant recipients proliferated normally to donor alloantigen in vitro, and produced IL-2, interferon-gamma, and IL-4 in amounts comparable to normal CD4 T cells. Tolerant recipients also developed a strong alloantibody response comprising both IgG1 (Th2-dependent) and IgG2b (Th1-dependent) subclasses. CONCLUSIONS: The results of this study suggest that the thymus, through the production of recent thymic emigrants, plays an important role in facilitating the induction of transplant tolerance after anti-CD4 mAb. Tolerant animals displayed strong cell-mediated and humoral alloimmune responses with no evidence of selective deviation from a Th1 to a Th2-like cytokine pattern.

Animals↗

PubMed1996

Alloantibody and intragraft cellular response to MHC class I-disparate kidney allografts in recipients tolerized by donor-specific transfusion and cyclosporine.

Congenic PVG.RT1u rats rapidly reject Aa class I-disparate kidney allografts from recombinant PVG R8 donors and we recently demonstrated that anti-class I MHC alloantibody plays a critical role in effecting acute rejection in this experimental model. In this article, we show that PVG.RT1u recipients can be rendered permanently and specifically tolerant to R8 kidney allografts by administration of four weekly donor-specific transfusions (DST) combined with a 7-day course of cyclosporine given with the first DST. Tolerance induction correlated with abrogation of a cytotoxic alloantibody response by thymus-independent, i.e., peripheral mechanisms; IgM and all IgG subclasses of anti-class I alloantibody were abolished. In contrast, nonrejecting kidney allografts in tolerant rats and rejecting grafts from unmodified recipients were similarly infiltrated by mononuclear cells, and intragraft transcripts for interleukin (IL)-2, interferon-gamma, and IL-13 were readily detected by reverse transcriptase polymerase chain reaction with no apparent quantitative difference between the two groups. Messenger RNA for IL-4 and IL-10 was present in rejecting grafts but barely detectable in grafts from tolerant animals. These results suggest that tolerance induction by DST and cyclosporine is, in this experimental model, associated with a selective impairment in humoral alloimmunity.

Animals↗

PubMed1996

Semantic and visual factors affecting the representation of map information.

In past research evidence has been found for both mental imagery and propositional hierarchies in subjects' map representations. How the visual and semantic factors associated with maps influence the use of one form of representation or another was the subject of the study reported here. Subjects were required to make relational judgments about city pairs. The results of experiment 1 indicated that superordinate relationships (the relationship of the counties of which the cities were members) affected only the most difficult perceptual judgments, but affected all judgments made from memory. Experiment 2 was done to determine the extent to which these findings were attributable to perceptual distortions rather than propositionally stored rules. Results of experiment 3 showed the degree of perceptual distinction necessary for propositional rules to have no significant influence on relational judgments.

Analysis of Variance↗